Effervescent barium sulfate-pectin x-ray contrast composition



Patentecl Nov. 17, 1953 EFFERVESCENT BARIUM SULFATE-PECTIN X-RAY CONTRAST COMPOSITION Elmer H. Slaybaugh, Parsons, Kans.

No Drawing. Application June 8, 1950, Serial No. 166,976

This invention relates to a composition in powder form for use in the fluoroscopic observa-,

the radiographic functions of barium sulphate to produce clearer and better radiographic depiction and to produce clearer pattern delineation of the mucosa and parts of the anatomy by providing a composition in powder form which when mixed with water will substantially immediately produce a homogeneous, mucilaginous liquid of such viscosity or density to form a stable suspension of the barium sulphate evenly distributed therein; to provide a composition in powder form consisting of pectin, barium sulphate, a sweetening material, a weak organic acid, and a salt of a strong base and weak acid in such proportions which when mixed with a suitable quantity of water or other suitable diluent will substantially immediately produce a mucilaginous liquid having a colloidal suspension of the pectin of such density that the barium sulphate is held in physical suspension; to provide a composition which when mixed with the correct proportion of water produces a mucilaginous suspension of barium sulphate having adesirable viscosity and a desirable pH which is miscible with the contents of the digestive tract without affecting its chemistry or producing adtional digestive function, is adherent to the rugae of the intestinal tract and gastroenteric mucosa because of the cohesive properties of the mucilaginous suspending agent which insures evenness of distribution of barium sulphate to photographic areas, is in fine evenly dispersed suspension insuring evenness of transit through the intestinal tract Without causing undue sagging or pocketing of barium salts in the loops of the intestines. or in the rugae of the intestinal tract, and which prevents any irritation to the rugae of the intestinal tract.

2- Claims. (Cl. 167-95 Another object of the invention is to prepare a composition in powder form consisting of barium sulphate, pectin, a sweetening agent, a weak organic acid, and a salt of a strong base and j weak acid in correct proportions which, when -mixed with'the correct proportion of water, re-

sults in reaction of the organic acid and the salt of the strong'base and weak acid which arelso adjusted relative to the pH of the pectinflthat when said reaction has reached its optimum there is an hydrogen ion concentration which dissolves or completes digestion of the pectin before it has time to settle and clump in a gummy mass; and to form a substantially permanent mucilaginous suspension of barium sulphate having a desired viscosity, the excess of hydrogen ion concentration or free acid being absorbed by the base whereby the pH of the mucilaginous suspension is within the range of 3 to G'and is such that no further hydrolysis or liquefaction is produced. i

Another object of the invention is toprepare a mixture which is quickly and easily prepared in less time and with less cost without requiring a preservative such as benzoic acid, for ready use, freely and readily miscible with the correct proportion of water and which retains its suspended state for long periods of time without undue settling, which is palatable, insuring patient comfort and cooperation, Which'is less constipating because of no sympathetic peristalsic reflex action on the duodenal mechanism impeding its transit through the system, and which obtains or produces effectiveness of opacity determined by measurements and .tests as conducted by the rmeter.

Another object of the invention i to provide a suspending agent in the form of pectin for barium sulphate which avoids any chemical action or interaction between the constituents such as would produce or create any poisonous substance injuriousto the human body when in use, and which will contain no possible soluble barium salts such as chlorides or sulphides or that when combined will produceany change which would result in the formation of poisonous compounds and is therefore stable, effective and unobjectionable for the reasons stated, and a perfect and safe preparation for use for the purposes stated, and is free from harsh or irritating gums or resins.

Another object of the inventionis to provide a formula consisting of barium sulphate, pectin, sodium carbonate, an organic acid such as citricor tartaric acid and'saccharin, in'which the sodium carbonate and organic acid are in correct chemical adjustment with a givenamount of pectin N. F., so that when the correct proportion of Water is added a hydrotropic factor is produced which reduces the pectin to agelatinous suspending property. a V

Other objects and advantages will be apparent from the following 'descriptionand formula.

I have found that commercial "pectin, namely termined by modern scientific methods. I have found that the higher the acid f actp or concentration of the solution,th e sily and quickly the pectin goes into oiiitiorfiid iiroduces a gel or emulsion. Also,,the highei; .,the acid factor or concentration below, Bthe thin er the emulsion and the less stableas the a'ci d due continues to react with the galacturoni es and increases esterification, the reactipn' continuing until complete hydrolysis occurs reie t e e i r. s c fi .e .b Qw ..-ih.a ssai'y" to form 'a suspension 'of barium"suln icri ah 'vis osity- H Composition of barium and; pectin mayjbe ax d he. ,form of 'i d idfi whichiithe m su hate a eeve i xg i i in s p o s. isc os sh P t nt. NQ- IZ 79 9 Y 1 i imil be b r diin .l bq a d j e h eand'-ma ke e i a qu d p ajpt ting afstorage and shipping problem, and' also 5 "1 1 3 va e, v

' 1nyention consists iii the preparationof riums'ulpliate-pectin composition in powder preferably in a 'd'egr ee of; fineness of iq'fto 1'15'0 "iiiesh'or finer, which, when mixed with water suitable *di luent, will quickly produce a ous suspension of barium sulphate hava Q sity, .th e pectinfand bariiim p ie-refiiaining in' suspension substantially 1s mnb ib p er. or efera ly onsists .of barium sulphate, pectm N, unsw et- "Len ing agenu aiweakjorganic acid such a tarc i iije de S lter a, weal: a i nd strong "base such flas sodiumfqarbonate, 1 iiim acetate, sodium citrate or sodium; bicarb'oiiat in correct' 'proportions,which," when vmixed as by stirringintothe correct ndent-ir te; cau e are water and liberating a weakrree' 'aCid'f'thConcentration of which causes suflicient pectin to be dissolved substantially immediately forming an emulsion sufficient to substantially suspend the barium sulphate in the solution. The weight 5 ratio of the barium sulphate and pectin pref- ;121Jp1(-;'iSjnth e order;of '38 'to 1 excess 'hydrogendon concentration remaining dissolves or completes digestion of the pectin before it or the barium has time to settle, the amounts of 10. eakgorganic acid and salt of the strong base k a'c id'being'such that when the reaction as ceased,the pH of the solution is such that tlgere Sis-substantial equilibrium whereby the ariu rn sulp hate and pectin are sustained in uspensidn""'with no liquefaction or hydrolysis. The composition, in powder form, made in accordance with the invention contains a suitable amount of barium 'su1phate and the formulas given hereinare based on a quantity of three zolgrm s gr ms)... bf -b r l l b Q The v 1 ofj'the"composition"are "prefe blyi 'pectinfhl. 39' to '70"grains and"hay ing La pl IIin fi' ouiic'es'offwalter in 'thefrange of {to 4.5, tartar acid" 4 "to: 6 grains, 's'odium"carb'onate 3am s'a'cchar n'up to 1 /2 a'i'iis, jaccordin'g'to'ithe s eeth'ess desired. lt'fi s 'pr'efh "enable. that jthe', i elatiye proportions of the tartaric "acid: and :sodium, car onate" be adjusted E q jdin i .t e HLQ the be ime t a 'W 30 the compjositionjis mixed with the proper amount ofwater, preferably fi' u .rne 'ately. apermane tmucilagifiousliquidsusoi bariu'nifsu hatejis rqmiedjsaidii'quid a'bH'in Uh asbeenifoun H t nge -1 added amo t, of ff reelac id is; supplied 'to n -1i asio e i a ra t T he. ffsa 't g ar ro h mixed and;keep' trituratingiuntil P s thmiieiha 93cc 1'5Q'mesh sieve. *The composition, in powder fOIZILIL'lSj thenpacked'in a 70 suitablecontainerfor shipping and istorage.

h g.-. iuprsa a ieeis vleii n rn for explanatory'purposes. It is 'dfto imit th'e manufacture of this m e mar nena .ifih fb w found that the "range of the proportion of-the The above it ingredients and the pH are critical. Therefore accurate controls and adjustments to obtain the proper'pH must be maintained. The resulting product, in powder form, when mixed with the proper amount of water, is a suspension of barium sulphate in a mucilaginous material. The result is a perfected and safe preparation 'of barium .sulphate powder in a finely dispersed, colloidal-like state of suspension, insuring better diagnostic accuracy in making possible more clear cut picture delineation. This preparation is especially prepared to meet the requirements in technique for depiction of the esophagus, rugae and gastroenteric mucosa, possessing both adhesive and cohesive properties and free from harsh or irritating gums or resins. The media insures moreclearly defined pictures when taking pictures of parts of the body by X-ray, or for fluoroscopic' examination and observation of the esophagus, the rugae of the intestinal tract and more distinct visualization of the gastroenteric mucosa and especially also of the rugae or folds of the intestines and as a distinct aid for rapid fluoroscopic observation, because it does not inte'rfere with normal anatomical functions either inthe upper or lower gastro tracts as it is properly adjusted whereby the pH or acidity is substantially that of the normal gastric acid secretion of an average person.

By way of clarifying an understanding of the invention, attention is directed to the fact that pectinum or pectin N. F. is authoritatively described as a purified carbohydrate product obtained from the dilute acid extract of citrus peal or apple pomace consisting chiefly of partially methoxylated polygalacturonic acids. A weak organic acid, for example tartaric acid or citric acid, and a salt of the strong base and weak acid, for example sodium carbonate, are reactors in proper chemical adjustment so that when water is added the reaction between the two salts produces a hydrotropic and/or chemotropic factor which quickly puts the pectin in solution producing a thin gel. This reaction produces a very slight effervescence which is due to the release of the carbon dioxide, however, the effervescen'ce is so slight that it performs no mechanical function as the dispersion is accomplished by stirring. The eifervescence ceases in a relatively short time, and after such cessation there is an excess of hydrogen ion concentration remaining which dissolves or completes digestion of the pectin before it has time to settle. The pH of the liquid is believed to be approximately 1.5 to 2.2 during the digestion of the pectin. The hydrogen ion concentration during the reversible reaction is such that suflicient pectin is digested and dissolved substantially immediately to suspend the amount of barium sulphate in the composition and there is not enough undissolved pectin remaining that will settle down to the bottom before the excess hydrogen ions will complete their digestion. The excess free acid unites with the salt of a strong base and weak acid after digestion of the pectin to form a stable suspension which does not hydrolyze or thin out. However, it has been found that if the reactors are adjusted to neutralize each other during the reaction, the pectin does not dissolve until after a number of hours.

The reactors do not react against or with the barium sulphate as determined by chemical assay and analysis for the possible presence of soluble barium salts, such as chlorides and sulphides also determined by acidifying with hydrochloric acid. Also, there is no indication that any, change has taken place or there is any possi-- bility of having any poisonous compounds formed. Therefore, the importance of the product is the fact that there is no chemical reaction or interaction between the tartaric acid and sodium carbonate with the barium sulphate.

A stabl composition is produced in the fact that the use of pectin in the manner and with. the ingredients shown will produce a suspending agent when water is added for the barium sulphate, that will not cause any injurious effect due to the chemical actions therein. The barium sulphate with a molecular weight of 233.42 when.

prepared with special care and subsequently purified, forms one of the most insoluble and also inert substances known to chemistry and is especially valuablein outlining the alimentary tract for X-ray work. It is insoluble in water, in organic solvents, and in aqueous dilute solutions of acid and alkalies.

The saccharin in the composition is used as a sweetening agent to insure a better state of palatability. There is no chemical action or interaction occurring between the saccharin and any of the ingredients.

The molecule of the natural high polymer pectin is composed principally of anhydrogalacturonic acid residues, partially methyl esterified and linked together to form a long chain. Nongalacturonide materials, galactan and araban ents merely acting as diluent.

The accelerated digestion time of pectin in my composition, on addition of water, is obtained by The first, the removal of" inactive constituents, It isassumed the gel formtwo separate actions.

ing ability of pectin is greater after the precipitation of the non-galacturonide material with the consequent increase in galacturonides. This can; be accomplished by two methods, by de-esterifi-- cation with enzymes whichis slow and although it reduces'the methyl ester groups, only partly reduces the non-galacturonides, or by the acid". method, which I use, in which a weak acid.. carbonic acid, at the proper pH, is introduced and the resulting hydrogen ion concentratiom partially removes the methyl ester groups and the non-galacturonides more rapidly and at approximately the same rate.

The two ingredients in my preferred formula which bring about the formation of carbonic acid are tartaric acid and sodium carbonate, the reaction, H2C4H4Os+Na2COs N32C4H4Os-i-H2CO, a simple form of double decomposition in which carbonic acid, one of the weakest and most unstable acids, breaks down in this method H2CO3 H2O+CO2, forming carbon dioxide and water. The important feature in this reaction is that the acid factor is present only long enough to accomplish the digestion of the pectin, and then is dissipated in the natural volatilization of carbon dioxide and any excess free acid is united with the sodium carbonate. Thus the reaction reaches its equilibrium after only a part of the methyl ester groups and non-galacturonide content has been de-esterified. If a strong acid were used and the action prolonged, the suspending qualities of pectin would be destroyed in proportion to the length of time the acid remains in ex cess.

Anot er action n m com sition which s eeds up; the solution of pectin is ,the hydrotropic, gor chemotropic factor involved, the tendency i cells. to :turnonmove in a certainflifectibn underthe influence of water or chemical: stimuli; It is the oxonium ion ,(HsO-H released inthe, reaction of the tartaric acid. and sodium carbonate whichcauses amovement of the water molecules toward the pectin molecules, thishmovement. exerting.

enough force to speed upthe process .ofdigestion or solvent properties of. v he. Water. proper chemical adjustment between. the reactors andthe pectin, the desiredend isjobtainedi It'is to :be seen that anadvantageof the come.

positioniis that it -may be made up and ikeptsin large quantities for immediate mixing and use with a diluent. Thus .it' will'be seen that Ijhaye testina-l tract; and gastroenteric mucosa and ,as,

anenem-a to produce contrasts for study and ,visual-izatioir-oi the lower bowel tract comprising, a mixture of the-following ingredientsand proportions, 'barium-sulphate, pectinNF'BO toI/IO grains, sodiumcarbonateflfi to 4 grains, and a dry organic acid-selectedfrom,,the.group con,- sisting of tartaric and citric aci dyeachbeingin a finely divided state;'Said:',c0mposition being characterized by the fact that when mired with water-the organic-aciisodimn carbonate and pectin react "to produce-a hydrogen ion concern: tration which accelerates digestion of the pectin whereby substantially immediately a viscous,

homogeneous, mucil'aginous, stabilized colloidal liquid is -formed -in which the barium sulphate.

and :pectin are sustained in suspension, said sodiumwarbonate and organic acid being adjusted n Q antity elative to thepH o the pectin in a selectediguantity ofwater wherebywhen the composition, is mixed "with'water and .reaction ceases thepI-I of the resulting solutionis in the range ofi3 to 6.,

ZJ'A, composition in dry powder form which when mixed with Water substantially immediate- 1y" forms a suspension of Jmedia to be used internally for fluoroscopic observations and roentgenographyof the'esophagus, rugae of the intestinal tract, and. gastroenteric mucosa and as an enema to produce contrasts for study and visualization of the lower .bowel tract comprising, :a mixture-0f. the following ingredients and .proportions, loariumsulphate 3ounces, pectin NF 4,6 grains, sodium carbonate 3.5 grains, saccharin lgrain and tartaric acid 5.6 grains, .each ingredient being in a finely divided state, said composition being characterized byv the fact that when mixed withwater the tartaric acid, sodium carbonateand pectin react to produce a hydrogen ion concentration whichaccelerates the digestion of the pectin whereby substantially'immediately a viscous, homogeneous, mucilaginous, stabilized colloidalliquid is formed in which the barium sulphate and pectin are sustained in suspension, said sodium carbonate and tartaric acid being adjusted in quantity relative-to the'pHof the pectin in a selected quantity of water, whereby when the composition is'mixed with water and reaction ceases the pH of the resultingsolution is in the range of 3 to 6."

H. SLAYBAUGH.

References Cited-'inthe file of this patent UNITED STATES PATENTS OTHEHREFERENCES 1 I-Iiss and Ebert, ,New ,Standard ,Formulary, 5th

Edition (1920), page 325. (Copy in Division .43.)

Journal of Obstetrics and Gynaecology of. the BritishEmpire, volume 51,'December,1 944 page 516. 

1. A COMPOSITION IN DRY POWDER FORM WHICH WHEN MIXED WITH WATER SUBSTANTIALLY IMMEDIATELY FORMS A SUSPENSION OF MEDIA TO BE USED INTERNALLY FOR FLUOROSCOPIC OBSERVATIONS AND ROENTGENOGRAPHY OF THE ESOPHAGUS, RUGAE OF THE INTESTINAL TRACT, AND GASTROENTERIC MUCOSA AND AS AN ENEMA TO PRODUCE CONTRASTS FOR STUDY AND VISUALIZATION OF THE LOWER BOWEL TRACT COMPRISING, A MIXTURE OF THE FOLLOWING INGREDIENTS AND PROPORTIONS, BARIUM SULPHATE, PECTIN NF 30 TO 70 GRAINS, SODIUM CARBONATE 2.5 TO 4 GRAINS, AND A DRY ORGANIC ACID SELECTED FROM THE GROUP CONSISTING OF TATRARIC AND CITRIC ACID, EACH BEING IN A FINELY DIVIDED STATE, SAID COMPOSITION BEING CHARACTERIZED BY THE FACT THAT WHEN MIXED WITH WATER THE ORGANIC ACID, SODIUM CARBONATE AND PECTIN REACT TO PRODUCE A HYDROGEN ION CONCENTRATION WHICH ACCELERATES DIGESTION OF THE PECTIN WHEREBY SUBSTANTIALLY IMMEDIATELY A VISCOUS, HOMOGENEOUS, MUCILAGINOUS, STABILIZED COLLOIDAL LIQUID IS FORMED IN WHICH THE BARIUM SULPHATE AND PECTIN ARE SUSTAINED IN SUSPENSION, SAID SODIUM CARBONATE AND ORGANIC ACID BEING ADJUSTED IN QUANTITY RELATIVE TO THE PH OF THE PECTIN IN A SELECTED QUANTITY OF WATER WHEREBY WHEN THE COMPOSITION IS MIXED WITH WATER AND REACTION CEASES THE PH OF THE RESULTING SOLUTION IS IN THE RANGE OF 3 TO
 6. 